tbuckley/cabot-search huggingface dataset:
Abstract 11206: Adipose-Derived Mesenchymal Stem Cells Overexpressing PD-L1 and Akt Confer Myocardial Protection Through Upregulation of CD25 <sup>+</sup> T Cells in a Rat Model of Acute Myocardial Infarction
Authors: Yu-Kai Lin, An-sheng Lee, Mei-Yao Wu, Chia-Ming Chang, Yun-Fang Chen, Yen-Nien Lin, Wei-Yu Chen, Woei-Cherng Shyu, Lien-Cheng Hsiao, Kuan-Cheng Chang
Journal: Circulation (2022)

Background: Translational studies showed positive results of stem cell therapy against myocardial infarction (MI)-induced cardiac dysfunction. Programmed death ligand 1 (PD-L1) is a key immune receptor, which modulates immune system and maintain the stability of coronary plaques. Akt is one of the signaling that exert its cardioprotective effect through regulating PD-L1. In the present study, we overexpressed PD-L1 and Akt in adipose-derived mesenchymal stem cells (AdMSC) and determined the protection against MI. Methods and Results: Adult Wistar rats were randomly separated into four groups: sham, MI, treatment of AdMSC or AdMSC overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) immediately after MI. MI was induced by LAD ligation and ADMSC were injected into the heart around the area at risk. After 4 weeks, rats were examined by echocardiography, pressure-volume analysis, infarct size measurement, and immunohistochemistry to evaluate the efficacy of the ADMSCs on myocardium. Results demonstrated AdMSC-PDL1-Akt was more resistant to ROS in vitro , and could restore MI-induced contractile dysfunction in vivo by increasing ESPVR (P=0.048) and PRSW (P=0.015). AdMSC-PDL1-Akt could also protect hearts from MI-increased infarct size (P=0.002). Immunohistochemistry staining with caspase 3 and NFκB were upregulated in MI hearts and significantly reversed in AdMSC-PDL1-Akt group (P&lt;0.001 and P=0.036). To clarify mechanisms underlying the effect of AdMSC-PDL1-Akt, we found it could induce normal T cells into CD25 + regulatory T cells in vitro , which is in parallel with the data shown in our in vivo immunohistochemistry study that CD25 was upregulated in AdMSC-PDL1-Akt tissues (P=0.03). Conclusions: Overexpression of PD-L1 and Akt in AdMSC could increase its resistance to ROS-related apoptosis in vitro and enhance the protective effects against MI-induced cardiac dysfunction through modulation of T cells in vivo . Keywords: AdMSC; PD-L1; myocardial infarction; regulatory T cells
Abstract 11737: Transhepatic Echocardiographic Approach Compared to the Subcostal Approach for Evaluation of the Inferior Vena Cava in Postoperative Patients With Cardiac Surgery
Authors: Dayana Orozco -Sepulveda, Oscar Lomeli Sanchez, Chen C Lin, Diego Alejandro Ramos Aguas, RAMON E SANTALO, Jorge Eduardo Hernandez del Rio, Tomas Miranda - Aquino
Journal: Circulation (2022)

Introduction: In postoperative cardiac surgery patients due to the presence of mediastinal tubes, evaluation of the IVC is complicated with the subcostal view, so the transhepatic view could be an option for its evaluation in these patients. Methods: We obtained a validation group of non-surgical patients and later in a group of postoperative cardiac surgery patients with mediastinal tubes. Measurements of the IVC diameter in both views was obtained. Agreement between measurements diameters, the time it took to obtain the images, the degree of pain and the quality of the echocardiographic image were compared. The agreement of the variables was determined by the Pearson test. Results: A total of 43 patients were obtained from the validation group and 49 patients from the group of postsurgical patients. In the validation group, no significant difference was found in the maximum diameter in subcostal vs. transhepatic (15.6 (± 6.1) vs 16.0 (± 6.2); p = 0.9, r = 0.93), neither in the minimum diameter (11.2 (± 6.8) vs 11.5 (± 6.8); p = 0.7, r = 0.94), nor at the time of execution of the images (15 (11-23) vs 10 (7 -21); p = 0.09, r = 0.17, neither in pain. The transhepatic view had a good image quality (98 % vs 85 %; p = 0.007). In the group of postsurgical patients, no significant difference was found in the maximum diameter in subcostal vs. transhepatic (18.3 (± 5.2) vs. 18.1 (± 4.8); p = 0.8, r = 0.90), neither in the minimum diameter (14.5 (± 5.4) vs 14.3 (± 7.2); p = 0.9, r = 0.93), the time to acquire the image was superior to the subcostal view (57s (40-83) vs 18s (12-32); p = &lt; 0.0001, r = 0.43); the subcostal view had an analogous visual scale of major pain (8 vs 0; p = &lt; 0.0001), transhepatic view had a better good image quality (96 % vs 40 %; p = &lt; 0.0001). Conclusions: In cardiac postoperative patients, it is possible to use the transhepatic view because it has an excellent agreement with the values of the subcostal window, with less time to obtain the images and with better image quality.
Abstract 11248: The Impact of Acute Coronary Syndrome on Early In-Stent Neoatherosclerosis Using Optical Coherence Tomography
Authors: Kazuhiro Nakao, Takanori Yamazaki, Yusuke Kure, Takenobu Shimada, Tomohiro Yamaguchi, Tsukasa Okai, Kenichiro Otsuka, Hiroaki Takeshita, Yasuhiro Izumiya, Daiju Fukuda
Journal: Circulation (2022)

Introduction: Patients with acute coronary syndromes (ACS) are known to have a higher risk of target vessel revascularization after percutaneous coronary intervention (PCI) and worse long-term prognosis than patients with stable angina. Neoatherosclerosis is one of the significant factors at very late stent thrombosis. And the presence of in-stent neoatherosclerosis is independently associated with major adverse cardiac event. Although many studies have been reported on neoatherosclerosis, few have been reported on short-term in-stent neoatherosclerosis. Moreover, none have evaluated the impact of ACS. We investigated the impact of ACS on in-stent neoatheroscrelosis using Optical Coherence Tomography (OCT) in the present study. Methods: From March 2017 to November 2020, we investigated 102 patients (122 lesions) who had undergone PCI using drug eluting stent during that period and were followed up for OCT within one year. Subjects were categorized as ACS or non-ACS according to clinical findings at the time of target lesion intervention. We used OCT to investigate the presence of early in-stent neoatherosclerosis. Result: ACS group consisted of 21 (20.6%). In patients with ACS, women tended to be more common (38% vs 19%, P =0.0777). There were no differences in age or presence of diabetes or dyslipidemia during treatment. There were also no significant differences in LDL-C levels at the time of PCI (88 (73-114) mg/dL vs 100 (85-124) mg/dL, P =0.319) and when observed by OCT (67 (55-81) mg/dL vs 68 (57-89) mg/dL, P =0.622). The ACS group was significantly more likely to have a previous history of ACS (38% vs 12%, P =0.0104). Stent length was significantly shorter in ACS patients (24 (18-28) mm vs 32 (23-38) mm, P =0.0365). The mean dulation from PCI was 292 days. In-stent neoatherosclerosis was more frequent in the ACS group (31.8 % vs 9.9 %, P =0.014). Conclusion: This observational study using OCT indicates that stenting for ACS lesion is associated with early in-stent neoatherosclerosis.
Abstract 11228: Association Between Nonalcoholic Fatty Liver Disease Risk Alleles and Atherosclerosis
Authors: Hiroaki Ikezaki, Ernst J Schaefer, Masayuki Murata, Nobuyuki Shimono
Journal: Circulation (2022)

Introduction: Nonalcoholic fatty liver disease (NAFLD) risk alleles are associated with lipid metabolisms. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD genetic risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,050 Japanese men and women (median age 55 years and median body mass index 22.9 kg/m2) free of cardiovascular disease, dyslipidemia, hypertension, and diabetes were studied. Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), glucokinase regulator ( GCKR ), and neurocan ( NCAN ) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, LDL-triglycerides, high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides, remnant-like particle cholesterol, lipoprotein(a), and adiponectin were also measured. At both baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed. Atherosclerosis was defined as cIMT more than 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and progression of atherosclerosis. Results: Both median and maximum cIMT of total participants did not differ between baseline and after a five-year follow-up. Among participants without atherosclerosis at baseline, the rate of plaque development was 13.8% (121/880) with the major allele (CC) of NCAN being significantly higher than other alleles. Variants of NCAN were associated with the development of plaque ( P = 0.04, Fisher’s exact test). Variants of PNPLA3 , TM6SF2 , GCKR , and NCAN were not associated with changes in lipoproteins. Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoproteins alterations among healthy Japanese participants.
Abstract 11328: Coronary Artery Calcium and Cardiovascular Outcomes in Patients With Diabetes: A Meta-Analysis
Authors: Chen-yu C Guo, Matthew Budoff
Journal: Circulation (2022)

Background: Presence of coronary artery calcium (CAC) has been demonstrated to increase mortality and major adverse cardiovascular events (MACE) in both diabetic and non-diabetic patients. A dose response relationship has been suggested between CAC score and cardiovascular outcomes. We performed a meta-analysis to compare the relative risk (RR) of mortality and MACE between categories of CAC scores in patients with diabetes. Methods: We searched the PubMed database to identify studies that investigated cardiovascular outcomes among diabetic patients with CAC. Only studies that used CAC=0 as reference group were included. We performed meta-analyses to obtain pooled RRs for mortality and MACE, as well as the composite outcome of both. Results: A total of 299 publications were identified and 6 studies (N=11,043) were included. With CAC=0 as the reference, CAC=1–100 has a RR of 1.64 (95% confidence interval: 1.34–1.99) for the composite outcome, 1.48 (1.18–1.87) for all-cause mortality, and 2.17 (1.47–3.19) for MACE. CAC=100–400 has a RR of 2.34 (1.9–2.9) for the composite outcome, 2.15 (1.67–2.78) for all-cause mortality, and 2.85 (1.94–4.21) for MACE. CAC&gt;400 has a RR of 3.78 (2.6–5.49) for the composite outcome, 3.29 (2.57–4.21) for all-cause mortality, and 5.87 (1.99–17.32) for MACE. Conclusion Among patients with diabetes, presence of CAC increases risk for both mortality and MACE, and higher CAC scores are associated with higher relative risk. CAC scoring is demonstrated to be a useful tool for prognostication and risk stratification among individuals with diabetes, and our analyses showed that even the pooled RRs of the lowest category had reached statistical significance.
Abstract 11143: Symptom Experience in Women With Ischemia and No Obstructive Coronary Artery Disease: A Mixed Methods Approach
Authors: Sneha Thandra, Esha K Dave, Scott Gaignard, Ana Leon, Arielle Schwartz, Melinda Higgins, Puja K Mehta, Laura P Kimble
Journal: Circulation (2022)

Introduction: Women with myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction, a condition associated with adverse cardiovascular outcomes. INOCA patients have recurrent chest pain and reduced quality of life, but therapeutic strategies to treat INOCA are poorly defined. In this study we used mixed methods to gain an understanding of their symptom patterns and burden clustered with other co-morbid conditions, while considering their overall symptom experience with having chronic angina. Methods: Twenty-four women diagnosed with INOCA based on coronary angiography were enrolled. Qualitative telephone interviews were conducted, recorded, and transcribed verbatim. First and second cycle coding was then used to analyze the qualitative data. Baseline demographics, risk factors, and angina burden by the Seattle Angina Questionnaire (SAQ) were assessed and descriptive statistics were performed. Results: Mean age was 53.2±10.8 years and body mass index was 30.8±6.9 kg/m 2 . Cardiac risk factors were prevalent with 43% hypertension, 57% hyperlipidemia, and 22% diabetes. SAQ scores indicated high angina burden and poor quality of life: 37.7±24.3 (physical limitation), 35.2±31.5 (angina stability), 41.3±23.2 (quality of life). Elemental qualitative coding and analysis identified four major themes: Invisible inscrutable threat, Longing for a normal/safe life, Rejecting labels, and “It has a toll”. A majority (75%) expressed both emotional burden and explicit frustration and dissatisfaction around their diagnosis. Conclusion: Qualitative and quantitative data supported that despite high symptom burden and poor quality of life, patients felt that they were frequently not believed, and that knowledge was limited to manage their condition. Research to close this persistent knowledge gap and to prioritize symptom management to help INOCA patients regain as much normalcy as possible is needed.
Abstract 11269: Comparing Measures of Adherence and Persistence to Ticagrelor Therapy in Patients With Acute Coronary Syndromes
Authors: Jungyeon Moon, Aya Ozaki, Dennis T Ko, Alice Chong, Jiming Fang, Peter Austin, Maneesh Sud, Cynthia Jackevicius
Journal: Circulation (2022)

Introduction: There have been efforts to accurately measure adherence to ticagrelor to identify suboptimal medication therapy in the first year post-ACS as nonadherence during this crucial period is a major obstacle to optimizing clinical outcomes. Our study aims to examine ticagrelor adherence and persistence using different methods to better understand adherence patterns. Methods: We conducted a retrospective cohort study of patients aged ≥65 years who had filled a ticagrelor prescription within 7 days post-ACS discharge in Ontario, Canada between 4/2014-3/2018. We estimated mean proportion of days covered [PDC], the proportion of patients with “good” adherence of PDC≥80%, both at 1 year and the proportion of patients who were persistently taking ticagrelor at 1-year, using permissible gaps between prescriptions of 3, 7, 14 and 30 days. Results: There were 9,763 ticagrelor users (mean age 73.6; 65.4% men). The mean 1-year PDC (±SD) was 80.8±29.2, while only 73.0% of the cohort showed good adherence (PDC≥80%). Using a permissible gap definition of 14 days, only 55.7% of patients were persistent with ticagrelor in the year post-ACS. The 1-year persistence rates were as high as 62.6% with an allowable gap of 30 days and as low as 49.7% for a 7-day gap and 39.3% for a 3-day gap. Conclusions: Adherence and persistence estimates varied widely based on the definition used. While the PDC estimates implied reasonable 1-year ticagrelor adherence, PDC methods overestimated continuous use of ticagrelor, yet persistence methods with small gaps were likely too stringent. Readers of adherence and persistence studies should pay close attention to the methods and definitions used.
Abstract 11473: An EHR-Based Machine Learning Model Predicts Myocardial Infarction Better Than an ECG-Based Machine Learning Model and the Pooled Cohort Equations
Authors: Linyuan Jing, John Pfeifer, Martin Kang, Dustin Hartzel, Sushravya Raghunath, Brandon Fornwalt, Christopher M Haggerty
Journal: Circulation (2022)

Introduction: Patients at high risk for myocardial infarction (MI) benefit from treatments designed for primary prevention, especially cholesterol lowering therapy. The pooled cohort equations (PCE) are the most commonly used risk predictor for future MI but show only modest performance. Hypothesis: Electronic health record (EHR)-based, and ECG-based machine learning models are better at predicting MI as compared toPCE. Methods: We retrospectively included all patients (age 40-79) with clinical encounters in Geisinger, having at least 1 clinically acquired ECG and no prior history of MI. Incident MI within 10 years of an index ECG was identified. The ability of 2 machine learning models to predict MI were compared to the PCE: 1) an XGBoost model with EHR data (age, sex, race, smoking history, vitals, 24 lab tests) as input features; and 2) a deep neural network (DNN) that used ECG traces, age, and sex as inputs. Models were compared based on area under the receiver operating characteristic curve (AUROC). Results: A total of 103,933 ECGs from 34,932 patients had sufficient follow-up, 21% of ECGs were followed by an MI event within 10 years. The EHR-based XGBoost model had the best performance (AUROC 81%) in comparison with both the ECG-based DNN model (AUROC 68%) and the PCE (AUROC 72%). 9% of the total encounters were predicted to be ‘high risk’ by the EHR-based model and not by the pooled cohort equations. In that subgroup, 60% of patients were not on a statin and the 10-year MI event rate was 26%. 20% of encounters were predicted to be ‘high risk’ by the PCE and not by the EHR-based model. The event rate in that subgroup was 12%. Conclusions: An EHR-based XGBoost model, but not an ECG-based DNN, is superior to the PCE in predicting future MI. Patients identified as high risk by the EHR-based model but missed by the PCE, have a high rate of future MI. Statin use in that group is low, suggesting ample opportunity for intervention.
Abstract 11646: Impact of Fetal Hypoxia on Myocardial Molecular Profile in the Lamb Extra-Uterine Environment for Neonatal Development
Authors: Jonathan J Edwards, Mallory Hunt, Yifan Yang, Spencer Williams, Caitlyn Bowman-Cornelius, Matthew Landell, Meredith Gunder, Jamuna Buchanan, Marcus Davey, Alan Flake, James W Gaynor, Zoltan Arany
Journal: Circulation (2022)

Background: Using the EXTrauterine Environment for Neonatal Development (EXTEND) system to chronically reduce myocardial oxygen delivery (DO 2 ) to levels mimicking human congenital heart disease caused increased myocardial capillarity and cardiomyocyte hypotrophy. However, molecular mechanisms for this have not been evaluated. Methods: Preterm fetal lambs were isolated by cesarean section and supported by EXTEND for 7 days in normoxia (n=5) or hypoxia (n=4) and compared to in utero gestational age matched controls (n=3). Right and left ventricle (RV, LV) molecular profiles were assessed by RNAseq, qPCR, and western blot. Differentially expressed genes (DEGs) were identified with limma/edgeR. BioPlanet enrichment analysis was performed with Enrichr. Results: DO 2 was lower in hypoxic lambs (15.5 vs 23.8 ml/kg/min, p&lt;0.0001). RNAseq revealed no significant DEGs between normoxia and control, while hypoxia significantly altered myocardial gene expression. The directionality was similar for LV and RV (r=0.82, p&lt;0.0001), but more statistically significant in LV (97 vs 7 DEGs, adj p&lt;0.05). Enrichment analysis revealed Hif1-target upregulation. qPCR confirmed upregulation of Hif1 targets and apoptosis activators Bnip3 (RV log 2 fold change (FC) 0.8) and Bnip3l (LV log 2 FC 1.6) and downregulation of the antiapoptotic Angpt1 (RV log 2 FC -1.5; all p&lt;0.05). However, by protein, Bnip3 and Bnip3l were reduced (RV FC 0.6, p&lt;0.0001) and (LV FC 0.8, p=0.0001), Bax was equally reduced (RV and LV FC 0.65, p&lt;0.05), and the proangiogenic/antiapoptotic hormone Angptl4 was increased (FC 1.9 RV and 2.3 LV, p&lt;0.05). In contrast, the proangiogenic/antiapoptotic cadherin receptor Cdh13 was reduced (RV and LV FC 0.5, p&lt;0.05). Finally, Fblim1 , a driver of cardiomyocyte hypertrophy, was decreased in LV and RV by RNAseq (logFC -0.75 and -0.63, adj p&lt;0.05) but increased by protein (LV FC 1.9, p=0.006). Conclusions: The normoxic EXTEND system faithfully recapitulates the myocardial molecular profile of normal lamb gestation. The molecular impact of fetal myocardial hypoxia is heterogeneous and suggests negative feedback loops with alterations in angiogenesis and cell survival/size. Future studies will dissect if these changes are sufficient to alter myocardial structure.
Abstract 11046: Hospital Initiative to Increase Plant-Predominant Foods and Nutritional Education
Authors: Sana Ahmad, Eugenia Gianos, Katrina Hartog, Nicole Roach, Sven Gierlinger, Bruno Tison
Journal: Circulation (2022)

Introduction: Due to reduction in cardiovascular risk, healthy, plant-based foods, as opposed to animal-derived products should be promoted to patients. We created a hospital initiative on the cardiac floors to educate the multidisciplinary staff to serve as advocates for healthy eating. Methods: Housestaff participated in education sessions on the benefits of plant-predominant meals and patient counseling. More plant-predominant options were added to the menu and several unhealthy items were eliminated. Food orders were assessed pre-intervention (February 2020) and post-staged interventions (October 2020 and April 2022). Food choices were assessed using the healthful and unhealthful diet index. Press Ganey scores were obtained and housestaff comfort with diet counseling was also assessed. Results: Resident perception of their own knowledge went from “poor” to “good” post-intervention. Confidence in talking to patients about plant-based diets went from “not confident at all” to “fairly confident". After analysis of diet orders, a 52% decrease was noted in animal-based products (chicken, beef, pork and turkey), 35% decrease in unhealthful food items (refined grains, processed foods, potatoes and sweetened beverages), and 25% decrease in plant-predominant food items (whole grains, fruits, vegetables, nuts, salads, legumes and fish), but this time period occurred in the setting of high COVID-19 rates. A subsequent analysis of a single cardiac unit after the COVID-19 surges and after select unhealthy items were removed from the menu showed notable improvements in each parameter when adjusted for discharges; a 2% increase in plant-based, 37% decrease in animal based and 4% decrease in unhealthy items. Press Ganey ratings for the quality of food increased post-initiative by at least 27%. Conclusions: This quality initiative was a local pilot to increase our understanding of interventions that may have a meaningful impact on healthy eating for patients. Interpretation of results is limited due to the COVID-19 pandemic, which may have impacted food choices of admitted patients. Although further research is needed, housestaff engagement may be a promising mechanism to educate patients and encourage food and nutrition changes in a health system.